The efficacy of diode laser and subgingival air polishing with erythritol in treatment of periodontitis (clinical and microbiological study).

BACKGROUND: There is insufficient clinical and microbiological evidence to support the use of diode laser and air-polishing with erythritol as supplements to scaling and root planning(SRP). The aim of the current study is to evaluate the clinical and microbiologic efficacy of erythritol subgingival air polishing and diode laser in treatment of periodontitis. METHODS: The study encompassed twenty-four individuals seeking periodontal therapy and diagnosed with stage I and stage II periodontitis. Eight patients simply underwent SRP. Eight more patients had SRP followed by erythritol subgingival air polishing, and eight patients had SRP followed by diode laser application. At baseline and six weeks, clinical periodontal parameters were measured, including Plaque Index (PI), Gingival Index (GI), periodontal Probing Depth (PPD), and Clinical Attachment Level (CAL). The bacterial count of Aggregatibacter actinomycetemcomitans(A.A), Porphyromonas gingivalis (P.G) was evaluated at different points of time. RESULTS: The microbiological assessment revealed significant differences in the count of A.A. between the laser and erythritol groups immediately after treatment, indicating a potential impact on microbial levels. However, the microbial levels showed fluctuations over the subsequent weeks, without statistically significant differences. Plaque indices significantly decreased post-treatment in all groups, with no significant inter-group differences. Gingival indices decreased, and the laser group showed lower values than erythritol and control groups. PPD and CAL decreased significantly across all groups, with the laser group exhibiting the lowest values. CONCLUSION: The supplementary use of diode laser and erythritol air polishing, alongside SRP, represents an expedited periodontal treatment modality. This approach leads to a reduction in bacteria and improvement in periodontal health. TRIAL REGISTRATION: This clinical trial was registered on Clinical Trials.gov (Registration ID: NCT06209554) and released on 08/01/2024.

Air-polishing followed by ultrasonic calculus removal for the treatment of gingivitis: A 12-month, split-mouth randomized controlled clinical trial.

OBJECTIVE: To evaluate the advantages of a novel protocol involving full-mouth erythritol-powder air-polishing followed by ultrasonic calculus removal in the maintenance of patients treated for gingivitis, with a focus on time and comfort. METHODS: Systemically healthy patients with gingivitis were selected. Following a split-mouth design, quadrants 1-4 and 2-3 were randomly allocated to receive air-polishing followed by ultrasonic calculus removal following a protocol known as Guided Biofilm Therapy (GBT) or traditional full-mouth ultrasonic debridement followed by polishing with a rubber cup and prophylactic paste (US + P). Bleeding on probing (BoP) and the plaque index (PI) were collected at baseline (T0), 2 weeks (T1), 4 weeks (T2), 3 months (T3), and 6 months (T4) and 12 months (T5). Following the same randomization, prophylactic therapy was provided at 3 months (T3) and 6 months (T4). Clinical parameters, treatment time and patient comfort and satisfaction were evaluated. RESULTS: A total of 41 patients were selected, 39 completed the study. The clinical parameters were clinically satisfactory for both treatments at every time. At 4 months after treatment, GBT maintained significantly lower BoP and PI. GBT protocol required a significantly lower treatment time, especially at T3 and T4, when it saved 24.5% and 25.1% of the time, respectively. Both treatments were rated positively by most patients. However, GBT was perceived as more comfortable, and a higher number of patients preferred it. CONCLUSION: No significant difference was observed between GBT and conventional ultrasonic debridement and rubber cup polishing in terms of BoP and PI levels. The GBT protocol allowed less time expenditure and higher patients' perceived comfort.

Erythritol powder airflow for the treatment of peri-implant mucositis: A randomized controlled clinical trial.

OBJECTIVES: Peri-implant mucositis is a biofilm-related, reversible inflammatory disease that can evolve into peri-implantitis if not adequately treated. The aim of the present randomized controlled clinical trial was to evaluate the efficacy of air-abrasive powder as compared to chlorhexidine (CHX) for the treatment of peri-implant mucositis, in terms of clinical and patient-reported outcomes (PROMs) and occurrence of peri-implantitis 12 months after treatment. METHODS: In the control group, full-mouth calculus and plaque removal was performed with ultrasound and manual devices, and a 1.0% CHX gel was applied; in the test group, supra- and subgingival biofilm removal was performed using erythritol powder with a dedicated nozzle and calculus removal was performed with ultrasonic instruments if needed. Bleeding and plaque indexes, peri-implant probing depth and tissue level were measured at 1 week, and 1, 3, 6 and 12 months after treatment, while PROMs were evaluated up to 7 days after treatment. RESULTS: Among 80 included implants, 70 were analysed at 12 months follow-up (30 in the test group, 40 in the control group, and 20 subjects). Success rates (implant-level) in terms of bleeding index were significantly different between the test (96.7%) and control group (92.5%); as for PROMs, only taste sensation was significantly better in the test group. The test group was significantly correlated to the smallest changes in peri-implant probing depth between baseline and 3 months. CONCLUSIONS: The study showed that both treatment strategies are effective. This suggests that the use of air-abrasive powders could be used as an alternative biofilm removal method instead of adjunctive treatments with antiseptics.

Evaluation of the adjunctive use of Er:YAG laser or erythritol powder air-polishing in the treatment of peri-implant mucositis: A randomized clinical trial.

AIM: To assess the efficacy of Er:YAG laser (ERL) and erythritol powder air-polishing (AP) in addition to the submarginal instrumentation in the non-surgical treatment of peri-implant mucositis (PM). MATERIALS AND METHODS: Patients with at least one implant diagnosed with PM were included in the present 6-month randomized clinical trial (RCT). Implants were randomly assigned to one of the three treatment groups after submarginal instrumentation: AP (test 1 group), ERL (test 2 group) or no adjunctive methods (control group). The primary and secondary outcomes were, respectively, bleeding on probing (BoP) reduction and, complete disease resolution (total absence of BoP) and probing pocket depth (PPD) changes. The patient and the implant were considered the statistical unit. A multivariate logistic regression analysis was performed. RESULTS: A total of 75 patients were enrolled in the study. At each time point, significant BoP and PPD reductions were observed within each group. Intergroup analysis did not show statistically significant differences. Complete disease resolution ranged between 29% and 31%. The logistic regression showed that supramucosal restoration margin, PPD < 4 mm and vestibular keratinized mucosa (KM) significantly influenced the probability to obtain treatment success. CONCLUSION: The adjunctive use of AP and ERL in PM non-surgical therapy does not seem to provide any significant or clinically relevant benefit in terms of BoP and PPD reductions and complete disease resolution, over the use of submarginal instrumentation alone. Baseline PPD < 4 mm, presence of buccal KM and supramucosal restoration margin may play a role in the complete resolution of PM.

Non-surgical treatment of peri-implantitis with and without erythritol air-polishing a 12-month randomized controlled trial.

BACKGROUND: A variety of interventions have been explored in the non-surgical management of peri-implantitis. In spite of extensive testing of various study protocols, effective treatments largely remain unavailable. The objective of the present 12-month single-centre, examiner-masked, randomized controlled clinical trial was to explore whether a low-abrasive erythritol air-polishing system produces added clinical benefit when used adjunctive to conventional non-surgical management of peri-implantitis and to record any associated patient-centered outcomes. METHODS: Forty-three patients with mild to severe peri-implantitis including at least one implant either received ultrasonic/curette subgingival instrumentation and erythritol air-polishing (test) or ultrasonic/curette instrumentation only (control) at baseline and at 3, 6, 9, and 12 months. Probing depth (PD), bleeding on probing (BoP), dental plaque, suppuration (SUP), crestal bone level (CBL), and peri-implant crevicular fluid (PCF) were recorded at baseline, 6 and 12 months. Visual Analogue Scale (VAS) scores were collected immediately following subgingival interventions at all time-points. RESULTS: A reduction in PD was observed from baseline to 6 months for the test (p = 0.006) and control (p < 0.001) and from baseline to 12 months for the control (p < 0.001). No intergroup differences were observed for primary outcome variables PD or CBL over time (p > 0.05). At 6 months, a intergroup difference in PCF was observed in favor of the test (p = 0.042). Moreover, a reduction in SUP from baseline to 6 and 12 months was observed in the test (p = 0.019). Overall, patients in the control group experienced less pain/discomfort compared with the test (p < 0.05), females reporting more pain/discomfort than males (p = 0.005). CONCLUSIONS: This study confirms that conventional non-surgical management of peri-implantitis produces limited clinical improvement. It is shown that an erythritol air-polishing system may not produce added clinical benefits when used adjunctive to conventional non-surgical management. In other words, neither approach effectively resolved peri-implantitis. Moreover, the erythritol air-polishing system produced added pain/discomfort particularly in female patients. TRIAL REGISTRATION: The clinical trial was prospectively registered in ClinicalTrials.gov with registration NCT04152668 (05/11/2019).

The efficacy of the adjunct use of subgingival air-polishing therapy with erythritol powder compared to conventional debridement alone during initial non-surgical periodontal therapy.

AIM: To assess the efficacy of the adjunct use of a subgingival erythritol powder air-polishing device (EPAP) in comparison to conventional subgingival instrumentation alone during initial non-surgical periodontal therapy. MATERIALS AND METHODS: Twenty-one patients with generalized Stages 2 and 3 grade B periodontitis were included in this single centre, single blinded, split-mouth, randomized clinical trial. Teeth on the control side were treated with conventional hand and ultrasonic instrumentation, while those on the contralateral test side was treated using EPAP as adjunct to conventional subgingival instrumentation with hand and ultrasonic instruments. Three months after initial instrumentation, persisting pockets of ≥4 mm were re-treated, in both control and test sides, again with the respective treatment approach-subgingival instrumentation alone on control, and subgingival instrumentation + EPAP on test side. Clinical parameters such as probing pocket depth (PPD), bleeding on probing, and relative attachment level were recorded at baseline and 3 and 6 months following the initial instrumentation. Subgingival plaque samples were collected at baseline, immediately post surgery, as well as at 1 week, 1 month, 3 months, and 6 months after initial instrumentation. RESULTS: In the test group after 6 months, a significantly larger number of initially deep pockets (PPD ≥ 5.5 mm) were reduced to shallow (PPD ≤ 3.4 mm), and a larger attachment gain was observed. No statistically significant microbiological differences could be found between test and control group. CONCLUSIONS: The results of the present study indicate that the adjunct use of subgingival airflow therapy with EPAP during initial non-surgical periodontal therapy might be beneficial in initially deep pockets (PPD ≥ 5.5 mm).

Effectiveness and Clinical Performance of Erythritol Air-Polishing in Non-Surgical Periodontal Therapy: A Systematic Review of Randomized Clinical Trials.

Background and objectives: The purpose of the present systematic review was to analyze the effectiveness of erythritol-based air-polishing in non-surgical periodontal therapy. Materials and methods: The protocol details were registered in the PROSPERO database (CRD42021267261). This review was conducted under the PRISMA guidelines. The electronic search was performed in PubMed, Scopus, and Web of Science databases to find relevant clinical trials published until January 2022. The inclusion criteria consisted of human clinical trials which reported the use of non-surgical periodontal treatment and erythritol air-polishing compared to non-surgical periodontal treatment alone in patients with good systemic health requiring treatment for periodontal disease. Results: 810 studies were imported into the Covidence Platform. Of these, seven clinical trials met the inclusion criteria. In active periodontal therapy, for PD (probing depth), CAL (clinical attachment level), and BOP (bleeding on probing), no statistical significance was achieved at 6 months follow-up. In supportive periodontal therapy for PD, CAL, and BOP, no statistical significance was achieved at 3 months follow-up. Conclusions: The findings suggest that erythritol air-polishing powder did not determine superior improvements of periodontal parameters compared to other non-surgical periodontal therapies. Future randomized clinical trials (RCTs) with calibrated protocols for diagnosis, therapeutic approaches, and longer follow-up are needed to draw a clear conclusion about the efficiency of erythritol air-polishing powder.

Erythritol-Enriched Air-Polishing Powder for the Surgical Treatment of Peri-Implantitis.

Peri-implantitis represents a major complication that can compromise the success and survival of implant-supported rehabilitations. Both surgical and nonsurgical treatment protocols were proposed to improve clinical parameters and to treat implants affected by peri-implantitis. A systematic review of the literature was performed on electronic databases. The use of air-polishing powder in surgical treatment of peri-implantitis was investigated. A total of five articles, of different study designs, were included in the review. A meta-analysis could not be performed. The data from included studies reported a substantial benefit of the use of air-polishing powders for the decontamination of implant surface in surgical protocols. A case report of guided bone regeneration in sites with implants affected by peri-implantitis was presented. Surgical treatment of peri-implantitis, though demanding and not supported by a wide scientific literature, could be considered a viable treatment option if an adequate decontamination of infected surfaces could be obtained.

Subgingival air-polishing with erythritol during periodontal maintenance: randomized clinical trial of twelve months.

OBJECTIVES: To evaluate repeated subgingival air-polishing in residual pockets with a new erythritol powder containing 0.3% chlorhexidine. MATERIAL AND METHODS: Single-centre, examiner masked, randomized clinical trial of 12 months with a two-arm, within-subject parallel design. Fifty patients in periodontal maintenance were monitored in 3-month intervals. At months 0, 3, 6 and 9, all sites presenting with a probing depth (PD) >4 mm were subject to subgingival air-polishing (test side) or ultrasonic debridement (control side). The primary endpoint was presence/absence of PD >4 mm after 12 months. RESULTS: Totally 6918 sites were monitored at baseline, 457 of them had a PD >4 mm (range 5-9 mm). The number of pockets >4 mm per subject, PD and bleeding on probing were significantly lower at month 12. Differences between test and control were not significant. There was a significant difference in favour of air-polishing for the perception of pain/discomfort. Differences of frequencies at >1000 and >100,000 cells/ml of six microorganisms between baseline and month 12 were not significant. At month 12, test sites were less frequently positive for Aggregatibacter actinomycetemcomitans at >1000 cells/ml than controls, and counts never exceeded 100,000 cells/ml. CONCLUSIONS: Repeated subgingival air-polishing reduced the number of pockets >4 mm similar to ultrasonic debridement. It was safe and induced less pain.

Effect of erythritol and xylitol on dental caries prevention in children.

OBJECTIVE: The aim of this study was to test the efficacy of long-term, daily intake of erythritol and xylitol candy, compared with sorbitol candy, on the development of enamel and dentin caries lesions. METHODS: The study was a double-blind randomized controlled prospective clinical trial. Altogether 485 primary school children, first- and second-graders at baseline, from southeastern Estonia participated in this 3-year intervention. Each child consumed four erythritol, xylitol or sorbitol (control) candies three times per school day. The daily intake of polyol was about 7.5 g. The International Caries Detection and Assessment System (ICDAS) was used in the clinical examinations by four calibrated examiners at baseline and at 12, 24 and 36 months. RESULTS: The annual examination analyses and the follow-up analyses confirmed that the number of dentin caries teeth and surfaces at 24 months follow-up and surfaces at 36 months follow-up was significantly lower in the mixed dentition in the erythritol group than in the xylitol or control group. Time of enamel/dentin caries lesions to develop and of dentin caries lesions to progress was significantly longer in the erythritol group compared to the sorbitol and xylitol groups. Also the increase in caries score was lower in the erythritol group than in the other groups. CONCLUSIONS: In the follow-up examinations, a lower number of dentin caries teeth and surfaces was found in the erythritol group than in the xylitol or control groups. Time to the development of caries lesions was longest in the erythritol group. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01062633.

Air powder waterjet technology using erythritol or glycine powders in periodontal or peri-implant prophylaxis and therapy: A consensus report of an expert meeting.

OBJECTIVES: To attain a collective expert opinion on the use of air powder waterjet technology (APWT) with erythritol and glycine powders in the prophylaxis and therapy of periodontal and peri-implant diseases. MATERIAL AND METHODS: In the first step, a modified one-round online Delphi survey including 44 five-point Likert scale questions was conducted among a group of 10 expert clinicians and researchers with thorough knowledge and experience in this topic. In the second step, the single questions and the survey results were discussed during a meeting, and consensus statements were formulated, respectively. RESULTS: An agreement was reached on most items, especially opinions supporting glycine and erythritol powders as favorable with respect to efficiency, safety, and comfort. More scientific evidence is needed to support the improvement in clinical attachment on teeth and implants, especially when APWT with erythritol is used. In addition, APWT needs more long-term evaluation and studies in terms of microbiome/microbiological effects as well as effects on the inflammatory response on natural teeth and implants, also in light of a guided biofilm therapy concept. CONCLUSIONS: In line with the expert opinions and supported by the evidence, it was concluded that the use of APWT with erythritol and glycine powders in nonsurgical periodontal and peri-implant therapy and prophylaxis is patient compliant and efficient.

Sugar substitutes on caries prevention in permanent teeth among children and adolescents: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to systematically review the effect of sugar substitute consumption on caries prevention in permanent teeth among children and adolescents. DATA: Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing the clinical effect of sugar substitutes (both high- and low-intensity sweeteners) in preventing caries in permanent teeth among children and adolescents aged 6-19 were included. SOURCES: A systematic search was conducted in three databases (PubMed, Web of Science and Embase) without any restrictions on publication year. STUDY SELECTION: The initial search found 1,859 items, and finally, 15 studies (11 RCTs and 4 CCTs) with a total of 6325 participants (age: 6-18 years) were included. The Cochrane risk-of-bias assessment tools were used for quality assessment. Most (80%, 12/15) were graded as having a 'moderate' or 'high' risk of bias. All trials investigated sugar alcohol, which is a low-intensity sweetener. Xylitol was the most commonly investigated (73.3%, 11/15), followed by sorbitol (46.7%, 7/15), and erythritol (13.3%, 2/15). Results of the meta-analysis showed that both xylitol (standardized mean difference [SMD]: -0.50, 95% confidence interval [CI] -0.85 to -0.16, P = 0.005) and sorbitol (SMD: -0.10, 95% CI: -0.19 to -0.01, P = 0.03) had a significant effect in preventing dental caries compared to no treatment/placebo. No clinical trials on high-intensity sweeteners such as aspartame and saccharin were found. CONCLUSION: The consumption of xylitol or sorbitol is potentially effective in preventing caries in permanent teeth among children and adolescents. No clinical evidence is available regarding the role of high-intensity sweeteners in caries prevention. CLINICAL SIGNIFICANCE: The use of xylitol or sorbitol as sugar substitutes has a beneficial effect in preventing dental caries among children and adolescents.

The caries-preventive effect of xylitol/maltitol and erythritol/maltitol lozenges: results of a double-blinded, cluster-randomized clinical trial in an area of natural fluoridation.

OBJECTIVE: Xylitol studies suggest caries reductions in the order of 50%. Based on animal/microbial studies, erythritol potentially has caries-preventive properties. However, clinical studies are required to confirm this. The aim of the study was to investigate the additional caries-preventive effect of xylitol/maltitol and erythritol/maltitol lozenges delivered at school, relative to controls receiving comprehensive prevention, in a low-caries prevalence population. METHODS: A 4-year, cluster-randomized, double-blinded clinical trial. Five hundred and seventy-nine 10-year-old consenting subjects from 21 schools were randomly assigned to one of five groups. Four groups used the lozenges on school days, in three teacher-supervised sessions daily, over 1 or 2 years. The daily amount was 4.7 g/4.6 g for xylitol/maltitol and 4.5 g/4.2 g for erythritol/maltitol. The groups received free examinations and care in the public health centre. Four hundred and ninety-six children were analysed. The main outcome measure was dentin caries increment based on a clinical examination at 4 years since the start. The groups were compared in relation to the increment using hierarchical logistic regression to adjust for potential clustering. RESULTS: Use of xylitol/maltitol or erythritol/maltitol lozenges did not result in caries reduction. A strong relationship between baseline caries prevalence and the 4-year increment was observed (OR = 7.38; 95% CI: 3.78-14.41). CONCLUSIONS: The results suggest that in relatively low-caries conditions the school-based use of xylitol/maltitol or erythritol/maltitol lozenges would not have additional caries-preventive effect when compared with comprehensive prevention.

Exploration of singular and synergistic effect of xylitol and erythritol on causative agents of dental caries.

Non-cariogenic sweet substances, like sugar alcohols, are used to decrease the risk of caries by reducing the growth of dental plaque. The aim of our study was to reveal the impact of xylitol and erythritol on the growth and biofilm formation of cariogenic bacteria including as a novelty, set of clinical mutans streptococci and Scardovia wiggsiae and to assess the possible synergistic influence of these polyols. We found both xylitol and erythritol to express high growth inhibition effect on cariogenic bacteria. In synergistic effect experiments, 10% polyol combination with excess of erythritol was found to be more effective against growth of Streptococcus mutans and the combination with excess of xylitol more effective against growth of Streptococcus sobrinus and S. wiggsiae. In biofilm inhibition experiments, solutions of 10% polyols in different combinations and 15% single polyols were equally effective against mutans streptococci. At the same time, higher biofilm formation of S. wiggsiae compared to experiments without polyols was detected in different polyol concentrations for up to 34%. In conclusion, both erythritol and xylitol as well as their combinations inhibit the growth of different cariogenic bacteria. Biofilm formation of mutans streptococci is also strongly inhibited. When applying polyols in caries prophylaxis, it is relevant to consider that the profile of pathogens in a particular patient may influence the effect of polyols used.

A salivary metabolite signature that reflects gingival host-microbe interactions: instability predicts gingivitis susceptibility.

Several proteins and peptides in saliva were shown to stimulate gingival wound repair, but the role of salivary metabolites in this process remains unexplored. In vitro gingival re-epithelialization kinetics were determined using unstimulated saliva samples from healthy individuals collected during an experimental gingivitis study. Elastic net regression with stability selection identified a specific metabolite signature in a training dataset that was associated with the observed re-epithelialization kinetics and enabled its prediction for all saliva samples obtained in the clinical study. This signature encompassed ten metabolites, including plasmalogens, diacylglycerol and amino acid derivatives, which reflect enhanced host-microbe interactions. This association is in agreement with the positive correlation of the metabolite signature with the individual's gingival bleeding index. Remarkably, intra-individual signature-variation over time was associated with elevated risk for gingivitis development. Unravelling how these metabolites stimulate wound repair could provide novel avenues towards therapeutic approaches in patients with impaired wound healing capacity.

A new multiple anti-infective non-surgical therapy in the treatment of peri-implantitis: a case series.

BACKGROUND: Peri-implantitis is a frequent disease that may lead to implant loss. The aim of this case series was to evaluate the clinical results of a new non-surgical treatment protocol. METHODS: Fifteen patients with dental implants affected by peri-implantitis were treated with a multiple anti-infective non-surgical treatment (MAINST) which included two steps: 1) supra-gingival decontamination of the lesion and sub-gingival treatment with a controlled-release topical doxycycline; 2) after one week, a session of supra and sub gingival air polishing with Erythritol powder and ultrasonic debridement (where calculus was present) of the whole oral cavity was performed along with a second application of topical doxycycline around the infected implant. Primary outcome measures were: implant failure; complications and adverse events; recurrence of peri-implantitis; secondary outcome measure were presence of Plaque (PI), Bleeding on Probing (BOP), Probing Pocket Depth (PPD). Recession (REC), Relative Attachment level (RAL). RESULTS: Neither implant failure nor complications nor adverse events were reported. Statistically (P<0.01) and clinically significant reductions between baseline and 1 year of PI (100% vs. 13.9%, 95% CI: 72.4% to 93.7%); BOP (98.5% vs. 4.5%, 95% CI: 85.4% to 98.5%) and PPD (7.89 vs. 3.16 mm, 95% CI: -5.67 to -3.77), were detected. At baseline, all 15 patients had a PPD>5 mm at the affected implant(s), whereas only 3.7% at 3-month follow-up a PPD>5 mm, and none at 6 and 12 months. CONCLUSIONS: Within the limits of this study, the MAINST protocol showed improvement of clinical parameters for the treatment of peri-implantitis, which were maintained for up to 12 months.

Rat hepatomas: chemotherapy with lycurim and pyrazofurin.

Hepatoma 8999 was sensitive to Lycurim [1,4-di-(methylsulfonyloxy-ethylamino)-1,4-dideoxy-ms-erythritol] with a mean lethal dose (LD50) of 8.1 X 10(-8) M for a 6-hour treatment in vitro. The drug dose lethal to 10% of the rats with Lycurim (10 mg/kg) injected ip 12 times into hepatoma 8999-bearing BUF rats at 10-day intervals provided a mean increase in life-span (ILS) of 156%. The more rapidly growing, less differentiated hepatoma 3924A was tenfold less sensitive to Lycurim in vitro, and three treatments in vivo (10 mg/kg given every 8 days) gave an ILS of only 18% in ACI/N rats. Because hepatoma 8999 had a high adenosine kinase activity, the effect of Pyrazofurin (PF; 3-beta-D-ribofuranosyl-4-hydroxypyrazole-5-carboxamide) was examined in vitro: The LD50 was 8.5 X 10(-8) M in a 6-hour exposure. In hepatoma 3924A, with a fifteenfold lower adenosine kinase, the LD50 was 22-fold higher. Three treatments with PF (4 mg/kg given every 2 days) in hepatoma 8999 caused an 18% ILS and no host toxicity, but in hepatoma 3924A no significant ILS was observed. Lycurim combined with PF (0.05 microM each) in hepatoma 8999 cells in vitro provided synergistic kill, but Lycurim and PF (0.3 and 1 microM, respectively) in hepatoma 3924A cells yielded summation. When 10 rats with hepatoma 8999 were treated 15 times with the optimal dose of Lycurim (7.5 mg/kg every 10 1/2 days), 1-year survivors numbered 7. Alternate doses of Lycurim (7.5 mg/kg) and PF (3 mg/kg) at 5-day intervals for 4 months to 10 rats gave an ILS of 152% with eight 1-year survivors and no host toxicity.